1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice

Aims: Acute pancreatitis (AP) is an inflammatory condition wherein pro-inflammatory mediators, oxidative stress, and NF-kappa B signaling play a key role. Currently, no specific therapy exists and treatment is mainly supportive and targeted to prevent local pancreatic injury and systemic inflammatory complications. This study was aimed to examine whether 1,8-cineole, a plant monoterpene with antioxidant and anti-inflammatory properties could ameliorate cerulein-induced acute pancreatitis. Main methods: AP was induced in Swiss mice by six one hourly injections of cerulein (50 mu g/kg, i.p.). 1,8-cineole (100, 200 and 400 mg/kg, p.o.) was administered 1 h prior to first cerulein injection, keeping vehicle and thalidomide treated groups as controls: Blood samples were taken 6-h later to determine serum levels of amylase and lipase, and cytokines. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) assays, reduced glutathione (GSH) levels, and for nuclear factor (NF)-kappa B immunostaining. Key findings: 1,8-cineole effectively reduced the cerulein-induced histological damage, pancreatic edema and NF-kappa B expression, levels of MPO activity and MDA, and replenished the GSH depletion. Cerulein increased serum levels of amylase and lipase, and pro-inflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 were also decreased by 1,8-cineole pretreatment, similar to thalidomide, a TNF-alpha inhibitor. The anti-inflammatory IL-10 cytokine level was, however, enhanced by 1,8-cineole. Significance: These findings indicate that 1,8-cineole can attenuate cerulein-induced AP via an anti-inflammatory mechanism and by combating oxidative stress. Further studies are needed to clearly elucidate its benefits in patients on acute pancreatitis. (C) 2013 Elsevier Inc. All rights reserved.